It sometimes seems that science progresses by the invention of new buzz words. For the last few years the newspapers have been full of talk about genomes, inspired by the effort (now reaching fruition), of sequencing the entire DNA sequence of humans. The Human Genome Project lead to many debates and articles about ownership: Who owns the genome? or words to similar effect, has been the title of many a polemic. In reality there is only one answer to that question: we do. That should have been the end of the story, but the tooth and claw of business soon entered the game and many companies have claimed intellectual property (polite talk for patents) on bits and pieces of the human genome. Just how many of these will stand up in court is another matter (why is it that lawyers always do well out of such disputes?).
The plot has thickened with the buzz word of 2001 stem cells; even President Bush has got into the act. Just what are stem cells? And what is all the fuss about?
The revolution in developmental biology, of which the science of embryology is but part, has been almost as dramatic as that of genomics in the last decade or so. Without wishing to get caught up in the arguments about genetic determinism, I will simply state two propositions: one, that the form and function of every cell in a human body (be it a muscle cell, a blood cell, a skin cell or a nerve), is determined by its genetic constitution; two, each of these cells have (within an individual) an identical genetic constitution, determined at the time the sperm and egg fuse to form the single-celled human embryo.
Yet, if genes determine form and function, how does two follow from one? The broad answer is simple: the variety of cell forms and functions result from differences in the way the genome is expressed in different cells. Determining how this happens has been, and remains, an issue at the cutting edge of the field of developmental biology. One can think of the general process as occurring in two stages: determination and differentiation. Cells are determined to develop into a particular type, e.g. muscle cells, well before they differentiate as such, a process that involves the synthesis of many proteins specific to muscle and leads to muscle cells having their characteristic contractile function.
Most of my cells, and yours, are fully differentiated. In many, though not all, cases this means that they no longer divide. But we all know that some tissues have the power to regenerate if lost or damaged the most obvious example is skin. Other cells, for example those that circulate in our blood, are continuously produced. But nerve cells, so central to our function, do not divide and are not reformed if lost, by disease or physical damage. For cells or tissues to be continuously produced there must be a population of undifferentiated dividing cells from which they can arise these are the notorious stem cells. They have been known to biologists for decades. So why the fuss now?
Pirating progress
About twenty years ago researchers such as Martin Evans in Cambridge discovered a way of deriving stem cells from early embryos of mammals in this case mice. These were (imaginatively) called embryonic stem cells (or ES cells for short). These cells are wholly undetermined and undifferentiated they can be induced to differentiate into any cell type of the body. It does not take long to see why this might be exciting could ES cells be used as a source of replacing organs and tissues for example nerves in the brain of a patient with severe neural degeneration (Alzheimers disease and new variant CJD, for example)? This indeed is the promise, though we must temper optimism and not expect miracles within the next decade.
Mice, of course, are not (quite) human (I write as a biologist). If ES cells can be made from mouse embryos can they be made from human embryos? The answer is yes, this breakthrough being made by James Thompson at the University of Wisconsin in Madison in 1998. It is these human ES cells about which all the fuss is being made. And fuss has come from two quarters.
The first group of fussers (entering from the far right) are those who, for whatever reason, object to the use of human embryos for scientific research. Unfortunately many of these are not content simply to refuse any therapy based on such research but attempt to prevent the research from proceeding. In the UK this research is permitted. In the US it is too, as long as it is not federally funded! Since the vast majority of biomedical research in the US is federally funded this has created something of a problem. With uncharacteristic guile Bush gave a great deal of thought to this issue and has come up with a compromise: federally funded researchers can use the stem cells, but only with those made before 9 August 2001 (the date of his television speech).
But if, before (or after) this date, federally funded US researchers could not make stem cells, what stem cells are they to use for their research after this date? Yup, got it in one: those made by private companies. But, if stem cell therapy really does live up to the hype can we really be comfortable with this technology being developed and owned by private companies? In fact the situation is worse, because James Thompson (the inventor of human ES cells) patented the technology or, rather, the Wisconsin Alumni Research Foundation did (they who brought you warfarin to kill rats or keep your blood from clotting).
Enter the second group of fussers, stage left. The WARF patent was licensed to a company in California called the Geron Corporation (they, as their name suggests, hope to make money by making us live longer). This patent license might not hinder academic scientific research too much, but will surely affect the progress of the application of this research, and hence is of great concern not only to the US National Institutes of Health (who will fund such public research as G. W. Bush and his right-wing fanatical cronies permit). To quote Sheryl Stolberg in the New York Times recently, there is a complex tangle of intellectual property rights and contracts covering stem cells involving the federal government, the University of Wisconsin and private companies.
The pragmatic issue is whether or not the progress of ES cell research and hence the promise of real progress in the treatment of many of the most intractable diseases and conditions will be seriously held back by these problems. But the more general issue is whether or not research of such high promise should be allowed to be dominated by a few commercial companies, particularly at such an early stage and so far from medical application. A very strong case can I would claim be made that progress in this field will be fastest if it can attract the best biomedical researchers of our time; and that this will only happen within a culture of open, rather than proprietary, science. This issue is too important to be left to scientists and lawyers. The time has come again to make your voice heard; the answer to the question is ours.
